Ideally, therapies designed to control pathogenic oral microorganisms will suppress or abolish those organisms, leaving a stable host-compatible microbiota in place. At times, however, attempts to eliminate periodontal pathogens lead to undesired changes in the microbiota. Two of the most obvious are overgrowth of pathogenic species not commonly found din high numbers in the oral microbiota and the emergence of antibiotic resistant species. This Project will be concerned with the safety of therapies, particularly antibiotic therapies, employed to control periodontal infections. The immediate goal is to determine the consequences of antibiotic therapy on the composition and antibiotic resistance of the periodontal microbiota. The first aim is to determine how antibiotic therapy shift the composition of the subgingival microbiota by monitoring levels of 120 bacterial species using Checkerboard hybridization. Subgingival species in pooled subgingival plaque samples will be examined at baseline, at the completion of therapy, and at 1-year post therapy for 24 subjects treated by either scaling and root planing (SCR), SCR plus local tetracycline, or SCR plus systemic amoxicillin and metronidazole. The second aim will determine how antibiotic therapy affects antibiotic resistance genotype and phenotype of plaque bacteria. Twelve subjects in the three groups described for Aim 1 will have 60 colonies picked for each time point. The isolates will be identified by Checkboard hybridization of 16S rRNA sequencing, and the antibiotic resistance genotype will be determined by Southern hybridization. Antibiotic resistance phenotype will be determined by plate culture. Species that are resistant to multiple antibiotics will be identified and made available to collaborators examining resistance genes.